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Among the diverse organosilicon compounds, Si-stereogenic silanes have recently demonstrated promising biological activities but only few protocols for the preparation of organosilicon compounds possessing a Si-stereogenic center exist in the literature. Here the authors show that a strong and confined Brønsted acid catalyzed enantioselective cyclization of bis(methallyl)silanes and provides enantioenriched Si-stereogenic silacycles.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Quantum dots encapsulated in a gold nanoshell provide a hybrid plasmonic–fluorescent emitter with increased stability against high power excitation or drastic changes in the environment.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Machine-learning-augmented single-nucleus transcriptomic analysis compared molecular landscapes of immature neurons in the mammalian hippocampus across species, highlighting human-specific gene expression but convergent biological processes.

ERα^vlVMH neurons mediate the inhibitory role of 17β-oestradiol on prolactin production, and this inhibition is lifted in lactating mice to promote lactation-associated metabolic adaptations.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Defective rhythmic metabolism is associated with high-fat diet feeding and obesity. The authors show that the clock gene BMAL1 drives paraventricular hypothalamic neuron activity via rhythmic GABAergic neurotransmission, and that this mediates diurnal metabolism and diet-induced obesity.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia.

Molecules that recapitulate the structure and prion-like activity of misfolded tau hold promise as more relevant models of pathological tau propagation. Now, the macrocyclization of short tau fragments affords proteomimetics that seed tau aggregation in cells and adopt a β-arch conformation resembling those found in filaments from patient-derived extracts.

SEC-MX enables simultaneous quantitative differential analysis of protein assembly states and post-translational modifications, shedding light on their complex interplay and on protein regulation beyond abundance measurements.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Ming-Rong Wang, Benjamin Berman and colleagues perform whole-exome sequencing and global methylation profiling on different tumor regions of esophageal squamous cell carcinoma. They find evidence for intratumoral heterogeneity and identify late driver mutations targeting oncogenes and early driver mutations occurring in tumor-suppressor genes.

DNA polymerase beta (Pol β) is the primary enzyme responsible for processing 1-nt gaps in chromatin during DNA repair. Here, the authors determine the kinetic and structural basis of gap-filling DNA synthesis in the nucleosome by Pol β, providing fundamental insight into DNA repair in chromatin.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

‘Small cell lung cancers do not respond well to immune checkpoint blockade therapy, due to the poor recruitment of CD8 + T cells to the tumours. Here authors show that via combining radiotherapy, PARP inhibitors and anti-PD-L1 treatments, T cell infiltration and function could be improved via mechanisms that increase the chemo-attractants CCL5 and CXCL10.

The changes in super-enhancer (SE) landscape of cancers are mainly attributed to cell-intrinsic genomic alterations. Here, the authors perform epigenomic profiling on primary colorectal cancers (CRCs) and their matched normal tissues and show that local tumour microenvironment induces a SE activation and that its target, PDZK1IP1 promotes CRC growth.

Certain specific antigens have been shown to activate T cells in an MHC independent manner. Here the authors show a phycoerythrin reactive mouse TCR which recognises native protein and characterise the molecular nature of this interaction and that this specific TCR can be selected in the thymus.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

X-ray and cryo-electron microscopy structures of fungal mitochondrial calcium uniporter proteins reveal a tetrameric architecture and shed light on the function of the channel.

The REX element is associated with long-range enhancer–promoter interactions.

During chronic but not acute inflammation, chromatin remodelling is influenced by nuclear autophagy through WSTF interaction with ATG8 in the nucleus, leading to WSTF nuclear export and its subsequent degradation.

Pan-cistrome of the maize leaf under well-watered and drought conditions profiled by haplotype-specific MOA-seq highlights the relevance of transcription factor binding QTLs for understanding phenotypic diversity in maize.

The use of lung and colonic organoid systems to assess the susceptibility of lung and gut cells to SARS-CoV-2 and to screen FDA-approved drugs that have antiviral activity against SARS-CoV-2 is demonstrated.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Melanocortin action is known to regulate body weight. Here the authors report that while inhibition of the hypothalamic melanocortin action leads to obesity in mice, chronic activation of melanocortin action is not sufficient to cause weight loss.

Harty and colleagues report that physiological microbial exposures in mice can enhance memory T cell presence in the brain and influence neurological disease outcomes.

Integrating remote sensing and eco-evolutionary theory, this study explains 80–84% of photosynthetic efficiency variation across ecosystems by incorporating plant traits such as chlorophyll and leaf longevity with climate data, highlighting the importance of these traits for global carbon modelling.